Decreased analyte transport through implanted membranes: differentiation of biofouling from tissue effects

Membrane biofouling and tissue changes in the foreign body response are known to cause detrimental reductions of analyte transport into implanted biosensors. The relative contribution of each phenomenon is unknown. Hollow fiber microdialysis probes were employed to assess the effect of subcutaneous implantation on glucose flux through polymeric membranes in rats over 8 days and to differentiate the transport effects of biofouling versus tissue changes. Three commercially available membranes were examined: poly(ether sulfone) (PES), polyacrylonitrile (PAN), and polycarbonate (PC). As measured by glucose recovery (the ratio of microdialysis glucose to blood glucose concentrations), transport through PES membranes was significantly less on day 2 than day 0 (39% decrease, p < 0.05) whereas PAN and PC showed no significant decreases in flux until day 8 (42 and 43%, respectively). Application of a transport model to glucose recovery data obtained before implantation in vivo and after explantation indicated that mass transport resistances originating from biofouling and tissue compartments increased between days 0 and 8. However, on average the biofouling layer adherent to the probe created substantially less resistance to glucose transport (12-24% of total) than did the tissue that surrounded the probe. These results suggested that future material developments for biosensors should be directed at understanding and modifying transport properties of tissues at the implant site.